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Keywords = Withania somnifera L.

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26 pages, 1184 KB  
Review
Nutraceutical Applications of Withania somnifera: The Scientific Knowledge for Rational Modern Use of the “Ayurvedic Adaptogen”
by Sudip Pandey, Poonam Pant, Giovanni Corbioli, Erica Bonazzi, Miluska Cisneros-Yupanqui, Paola Salmaso and Stefano Dall’Acqua
Foods 2026, 15(12), 2192; https://doi.org/10.3390/foods15122192 - 17 Jun 2026
Viewed by 213
Abstract
Withania somnifera L. (Dunal), commonly known as Ashwagandha, is widely used in traditional medical systems, particularly Ayurveda, and is increasingly included in nutraceuticals and dietary supplements. This narrative review summarizes and critically discusses the literature published from 2015 to 2026 on WS, with [...] Read more.
Withania somnifera L. (Dunal), commonly known as Ashwagandha, is widely used in traditional medical systems, particularly Ayurveda, and is increasingly included in nutraceuticals and dietary supplements. This narrative review summarizes and critically discusses the literature published from 2015 to 2026 on WS, with a focus on CNS-related outcomes, proposed mechanisms, extract standardization, dosage, and safety considerations. Evidence from preclinical research and human studies suggests that WS preparations may influence stress-related and sleep-related outcomes and support neuroprotective pathways suggesting a significant role in nutraceuticals; however, the overall strength of evidence varies across indications and products, and heterogeneity in extract composition and study design limits firm conclusions. Further well-designed, adequately powered clinical trials using standardized preparations are needed to clarify efficacy, mechanisms of action, and long-term safety. Full article
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17 pages, 571 KB  
Article
Withanolides Are Detected in Human Urine Following Oral Administration of a Withania somnifera Product
by Alex B. Speers, Ellala D. Limoico, Axel Lozano-Ortiz, Luke Marney, Jaewoo Choi, Sarah A. Barr, R. Thomas Williamson, Wendy K. Strangman, Claudia S. Maier and Amala Soumyanath
Int. J. Mol. Sci. 2026, 27(12), 5289; https://doi.org/10.3390/ijms27125289 - 11 Jun 2026
Viewed by 266
Abstract
Ashwagandha (Withania somnifera (L.) Dunal; WS) is an adaptogenic herb, widely used in botanical dietary supplements. Plasma pharmacokinetics of selected withanolides, an important group of bioactive phytochemicals found in WS, have been described but no previous reports were found on their urinary [...] Read more.
Ashwagandha (Withania somnifera (L.) Dunal; WS) is an adaptogenic herb, widely used in botanical dietary supplements. Plasma pharmacokinetics of selected withanolides, an important group of bioactive phytochemicals found in WS, have been described but no previous reports were found on their urinary excretion following WS ingestion. Healthy, older adults were administered oral doses of 240 or 480 mg of Shoden®, a commercial extract of WS roots and leaves, and urine was collected over the subsequent 12 h. Using validated methods employing liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM-MS), we analyzed Shoden® and participant urine samples for the presence of 11 withanolides for which standards were available. Only withaferin A (0.09 µmol/mg Shoden®), withanoside IV (0.03 µmol/mg Shoden®), and a mixture of 2,3-didehydrosomnifericin and 3R-viscosalactone B (0.19 µmol/mg Shoden®) were present in Shoden® powder in amounts greater than 0.01 µmol/mg Shoden®. We detected four withanolides in participant urine: withaferin A; sominone, the aglycone of withanoside IV; 3R-viscosalactone B; and an abundant unidentified metabolite (WFNX), isomeric with 4-oxo withaferin A, and not detected in Shoden®. Urinary recovery of the other 3 detected compounds was generally low (<3% of the amount in Shoden®). These results provide new insights into the oral absorption, metabolism, and urinary excretion of withanolides found in WS and highlight additional withanolides to consider in future human pharmacokinetic and bioactivity studies of WS products. Full article
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17 pages, 317 KB  
Article
Nutraceutical Supplementation + Holstein Feed Surplus in Rams: Corporal, Metabolic, and Testicular Volumetry-Sperm Variables; The Robin Hood Effect
by Ángeles De Santiago-Miramontes, Andrés J. Rodríguez-Sánchez, César A. Meza-Herrera, Ulises Macías-Cruz, Karla Q. Ramírez-Uranga, Cayetano Navarrete-Molina, Pablo Arenas-Báez, Mayela Rodríguez-González, María A. Sariñana-Navarrete and Edgar Díaz-Rojas
Vet. Sci. 2026, 13(5), 440; https://doi.org/10.3390/vetsci13050440 - 30 Apr 2026
Viewed by 1144
Abstract
Nowadays, it is central to generate innovations that convert agricultural by-products and food waste into valuable animal products while promoting the long-term resilience and sustainability of vulnerable animal production systems. Nutraceuticals (i.e., ‘nutrition + pharmaceutical’) are derived from foods that offer health benefits. [...] Read more.
Nowadays, it is central to generate innovations that convert agricultural by-products and food waste into valuable animal products while promoting the long-term resilience and sustainability of vulnerable animal production systems. Nutraceuticals (i.e., ‘nutrition + pharmaceutical’) are derived from foods that offer health benefits. In animal production, nutraceutical supplementation with Withania somnifera and Lepidium meyenii has shown positive effects on the endocrine, cardiopulmonary, and central nervous systems. We aimed to evaluate the possible impact of nutraceutical supplementation on rams fed a diet based on surplus feed from a highly industrialized Holstein cow production system, on corporal (live weight [LW], kg; body condition score [BCS], units), metabolic (blood glucose [GLU], mg dL−1; serum protein [PRO], g 100 mL−1), and sexual–testicular variables [sexual odor (ODOR, units); scrotal circumference (SC, cm); testicular volumes (TVOL, cm3); and estimated daily sperm production (EDSP, millions)]. Black Belly rams (n = 12; LW = 70.36 ± 1.2 kg; BCS = 2.96 ± 0.03 units; age = 3.8 ± 0.2 years; 25° N) were divided into 3 experimental groups: (1) WITH, supplemented with Withania somnifera (400 mg kg−1 LW d−1); (2) LEPI, supplemented with Lepidium meyenii (400 mg kg−1 LW d−1); and (3) CONT, not supplemented. The variables LW, BCS, GLU, PRO, and SC, as well as some components of TVOL, did not differ (p > 0.05) among the main effects of treatment or time; only ODOR, right transverse testicular diameter, and total testicular volume differed among treatments, generally favoring the WITH group. Furthermore, the TRT × T interaction demonstrated superior performance (p < 0.05) in the WITH group, with the largest values for LW, GLU, PRO, ODOR, SC, width of the right testicle, volume of the right testicle, total testicular volume, and EDSP. From a productive–reproductive perspective, the Robin Hood Effect—through the use of rejected dairy cattle rations as the base diet for rams—and supplemented with nutraceuticals (WITH and LEPI), emerges as a viable alternative to improve not only the productive–reproductive performance of Black Belly rams, but also other productive and socioeconomic outcomes; the latter contributing to the strengthening of producer and family well-being. Full article
19 pages, 4339 KB  
Article
Cytotoxic Potential Evaluation of Innovative Pressurised Cyclic Solid–Liquid Extracts from Withania somnifera
by Rosanna Culurciello, Karen Power, Sergio Esposito, Ilaria Di Nardo, Simone Landi, Gionata De Vico, Domenico Palatucci, Elio Pizzo, Daniele Naviglio and Armando Zarrelli
Plants 2026, 15(7), 1027; https://doi.org/10.3390/plants15071027 - 26 Mar 2026
Viewed by 644
Abstract
Ethnopharmacological relevance. Withania somnifera (L.) Dunal, widely used in traditional medical systems such as Ayurveda, Unani, and Middle Eastern folk medicine, is valued for its adaptogenic, anti-inflammatory, neuroprotective, antimicrobial, and anticancer properties. These activities are primarily attributed to withanolides, with Withaferin A recognized [...] Read more.
Ethnopharmacological relevance. Withania somnifera (L.) Dunal, widely used in traditional medical systems such as Ayurveda, Unani, and Middle Eastern folk medicine, is valued for its adaptogenic, anti-inflammatory, neuroprotective, antimicrobial, and anticancer properties. These activities are primarily attributed to withanolides, with Withaferin A recognized as one of the most bioactive constituents. Although traditional preparations often rely on the root, leaf use provides a more sustainable alternative and may yield significant quantities of active metabolites. Identifying efficient, modern extraction technologies that can enhance the recovery of bioactive compounds from leaves is essential for developing effective, standardized ethnopharmacological formulations. Materials and methods. Plants of W. somnifera grown from seeds were subjected to different environmental conditions (control, drought, cold, yeast extract treatment). Leaves were extracted using Pressurized Cyclic Solid–Liquid Extraction (PCSLE) with hydroalcoholic solvents and compared with conventional infusion of dried leaves. Extracts were fractionated with solvents of varying polarity and analyzed by TLC, HPLC, and NMR for quantification of Withaferin A. Expression levels of key withanolide-biosynthetic genes (CAS, SMT1, DWARF1, CYP71, CYP76) were assessed using qRT-PCR. Antimicrobial activity of pure Withaferin A, aqueous extract, and hydroalcoholic PCSLE extract was evaluated through MIC and MBC assays against Gram-positive and Gram-negative strains. Cytotoxic activity was measured via MTT assays in six human cancer cell lines after 3, 6, and 24 h of treatment. Results. PCSLE yielded substantially higher levels of Withaferin A than traditional infusion, especially in medium-polarity fractions (chloroform and ethyl acetate), with concentrations reaching 0.70% in fresh leaf mass (4.8% dry weight), compared to 0.11% obtained by infusion. Gene expression analysis revealed that 24-week-old plants exhibited the highest transcription of withanolide-biosynthetic genes, and drought stress significantly upregulated CAS, SMT1, DWARF1, CYP71, and CYP716, indicating enhanced metabolic flux toward withanolide production. Hydroalcoholic PCSLE extracts showed broad-spectrum antimicrobial activity, with MIC and MBC values comparable to pure Withaferin A and demonstrating bactericidal effects against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes. The aqueous extract showed activity only against Gram-positive strains. Cytotoxicity assays demonstrated an optimistic, dose-dependent reduction in cell viability across all tumour cell lines treated with the hydroalcoholic PCSLE extract, closely mirroring the activity of pure Withaferin A and consistently exceeding the effect of the aqueous extract. IC50 values confirmed the high bioactive content of PCSLE extracts and suggested mechanisms like those known for Withaferin A. Conclusions. PCSLE proved to be a highly efficient extraction technology for obtaining leaf extracts rich in Withaferin A, outperforming conventional extraction methods while exploiting sustainable plant tissue. Developmental stage and drought stress significantly modulated the expression of genes involved in withanolide biosynthesis, highlighting agronomic strategies capable of enhancing metabolite production. Hydroalcoholic PCSLE extracts exhibited antimicrobial and cytotoxic activities comparable to pure Withaferin A, supporting their relevance as promising therapeutic candidates. These findings advocate for the use of W. somnifera leaves as a sustainable source of bioactive compounds and demonstrate that advanced extraction technologies can contribute to the development of innovative ethnopharmacological preparations for antimicrobial and anticancer applications. Full article
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24 pages, 592 KB  
Review
The Clinical Implications of Ashwagandha (Withania somnifera L.) with a Special Reference to Side Effects—A Review
by Kaj Winther
Nutrients 2026, 18(5), 871; https://doi.org/10.3390/nu18050871 - 9 Mar 2026
Viewed by 3081
Abstract
Ashwagandha (Withania somnifera L.) root powder and extracts have long been used in Ayurvedic medicine to improve sleep and anxiety. Recent scientific investigations into its efficacy have shown promise for relief from anxiety, insomnia and stress and for improving the immune system. [...] Read more.
Ashwagandha (Withania somnifera L.) root powder and extracts have long been used in Ayurvedic medicine to improve sleep and anxiety. Recent scientific investigations into its efficacy have shown promise for relief from anxiety, insomnia and stress and for improving the immune system. It has also been suggested that oxygen uptake in the cardiovascular system, muscle strength, cognitive function, the reproductive system and the aging process significantly benefit from ashwagandha treatment. Since the herbal remedy is taken daily by millions of people in India, China and parts of the West, it is interesting that there are very few case reports of side effects directly attributed to the treatment, suggesting that the administration of ashwagandha preparations may be safe. Currently, neither the European Medicines Agency nor the FDA considers ashwagandha as a drug or general health supplement. Therefore, ashwagandha products are marketed in the West as dietary supplements so that users may be exposed to unscrupulous vendors. In this narrative/literature review, scientific findings from basic research and human clinical trials on herbal remedies, spanning the period from 1994 to date, were critically evaluated for the purpose of highlighting knowledge gaps to provide context for new research. Such investigations will provide evidence for the efficacy and safety of ashwagandha treatment, thus making the herbal preparations more accessible to a wider audience. Full article
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14 pages, 275 KB  
Review
The Role of Nutraceuticals and Phytotherapy in Andrological Diseases: Tips and Tricks for Everyday Clinical Practice
by Andrea Abramo, Tommaso Ceccato, Simone Botti, Daniele Mattevi, Nicola Mondaini, Luca Gallelli, Truls E. Bjerklund Johansen, Michele Rizzo, Giovanni Liguori, Alessandro Zucchi, Alessandro Palmieri, Luca Boeri and Tommaso Cai
Uro 2026, 6(1), 4; https://doi.org/10.3390/uro6010004 - 30 Jan 2026
Viewed by 1799
Abstract
Background/Objectives: Interest in the use of nutraceuticals and phytotherapy for the management of andrological diseases has increased markedly in recent years. In particular, growing attention has been directed toward the treatment of patients affected by erectile dysfunction (ED), male infertility, chronic prostatitis/chronic [...] Read more.
Background/Objectives: Interest in the use of nutraceuticals and phytotherapy for the management of andrological diseases has increased markedly in recent years. In particular, growing attention has been directed toward the treatment of patients affected by erectile dysfunction (ED), male infertility, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and induratio penis plastica (IPP). However, several areas of uncertainty remain. This narrative review aims to examine the role of nutraceuticals and phytotherapeutic agents in the management of andrological disorders. Methods: A narrative review was conducted using PubMed, Scopus, Cochrane CENTRAL, and EMBASE to identify relevant studies published over the past 25 years. Only articles published in English and involving adult populations were included in the analysis. Results: Nutraceuticals and phytotherapeutic compounds have been extensively investigated in the current literature, and certain formulations—particularly specific combinations—have been evaluated in high-quality studies. Conversely, other compounds lack sufficient scientific evidence and therefore should not be recommended in routine clinical practice. In the management of ED, the following compounds, administered either alone or in combination, have demonstrated clinically significant effects: Panax ginseng, Tribulus terrestris, L-arginine, and Withania somnifera. L-carnitine, combined with micronutrients, antioxidants, and various traditional herbal supplements, appears to be an effective therapeutic option for male infertility and subfertility. Pollen extracts play an important role in the management of CP/CPPS, while carnitine, coenzyme Q10, silymarin, bromelain, and curcumin show promising potential in the treatment of IPP. Conclusions: Nutraceuticals and phytotherapeutic agents may provide favorable outcomes in the management of andrological diseases. Although current evidence is encouraging, larger prospective studies employing standardized protocols and treatment schedules are required to confirm long-term efficacy and to optimize therapeutic strategies. Full article
38 pages, 867 KB  
Review
Medicinal Plants for Child Mental Health: Clinical Insights, Active Compounds, and Perspectives for Rational Use
by Giovanna Rigillo, Joan M. C. Blom, Arianna Cocchi, Valentina Martinucci, Francesca Favaro, Giulia Baini, Giorgio Cappellucci, Fabio Tascedda and Marco Biagi
Children 2025, 12(9), 1142; https://doi.org/10.3390/children12091142 - 28 Aug 2025
Cited by 4 | Viewed by 8193
Abstract
Background/Objectives: Anxiety, agitation, and mood disturbances are increasingly common among children and adolescents. Given the limitations of conventional pharmacological treatments in the pediatric population, particularly for subthreshold or mild conditions, interest in complementary approaches such as phytotherapy is growing. This review aims to [...] Read more.
Background/Objectives: Anxiety, agitation, and mood disturbances are increasingly common among children and adolescents. Given the limitations of conventional pharmacological treatments in the pediatric population, particularly for subthreshold or mild conditions, interest in complementary approaches such as phytotherapy is growing. This review aims to critically evaluate the clinical evidence supporting the use of herbal medicines and botanical food supplements for mental health symptoms in youths and to explore the pharmacological basis of their activity. Methods: A systematic search was conducted across main databases for clinical trials involving herbal products for psychologically related symptoms in children and adolescents. Eligible studies included those using registered herbal medicines, as well as authorized food supplements, that evaluated behavioral or cognitive outcomes. In addition, bioinformatic analyses were performed on selected phytocompounds to predict their molecular targets. Results: Twenty-nine clinical trials were identified, including eighteen targeting pathological conditions (notably attention deficit/hyperactivity disorder (ADHD), anxiety, and depression) and eleven addressing borderline symptoms such as nervous agitation, restlessness, or sleep disturbances. Herbal products showing clinical promise include Bacopa monnieri (L.) Wettst., Crocus sativus L., Ginkgo biloba L., Hypericum perforatum L., Lavandula angustifolia Mill., Melissa officinalis L., Panax ginseng C.A. Meyer, Passiflora incarnata L., Pinus pinaster Aiton, Valeriana officinalis L., and Withania somnifera (L.) Dunal. Bioinformatic predictions revealed polypharmacological activity profiles involving neuroinflammatory, neuroprotective, and neurotransmitter-related pathways. Conclusions: This review highlights both the potential and the current limitations of herbal products in pediatric mental health care. Evidence supports their use for selected indications, provided that standardized preparations and clinical oversight are ensured. Further research is essential, particularly to inform dosing, safety, and integrative care strategies. Full article
(This article belongs to the Special Issue Advances in Mental Health and Well-Being in Children (2nd Edition))
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24 pages, 7673 KB  
Article
Development, Molecular Docking, and Anti-Anemia Potential of Polyherbal Formulation
by Deepak Bharati, Sakshi Nirhali, Abhijeet Puri, Popat Mohite and Sudarshan Singh
Biology 2025, 14(8), 1052; https://doi.org/10.3390/biology14081052 - 14 Aug 2025
Cited by 2 | Viewed by 2817
Abstract
Anemia remains a widespread public health concern, and the search for interventions demonstrating potent anti-anemic activity is critical for reducing its impact among high-risk populations. Conventional iron therapies are associated with several complications and potential adverse effects. This study explored a polyherbal approach [...] Read more.
Anemia remains a widespread public health concern, and the search for interventions demonstrating potent anti-anemic activity is critical for reducing its impact among high-risk populations. Conventional iron therapies are associated with several complications and potential adverse effects. This study explored a polyherbal approach to develop a safer and more effective alternative treatment for anemia. A molecular docking study was initially performed to screen and evaluate alizarin, catechin, kaempferol, recesmol, rubiadin, and rutin, which are known for their antioxidant and hematinic potential. Using AutoDock Vina, these compounds were docked against the target protein (PDB ID: 6MOE) with EPE and ferrous ions as controls. Rutin demonstrated the highest binding affinity of −6.4 kcal/moL, whereas alizarin and rubiadin both followed closely with −6.3 kcal/moL, while kaempferol and ellagic acid exhibited a binding affinity of −6.2 kcal/moL. In comparison, the reference compounds tested ferrous ions, and native ligand EPE (−5.0 kcal/moL) and iron (−4.8 kcal/moL), showed mild affinities. Moreover, the tested compounds demonstrated stable binding, suggesting their potential relevance in modulating anemia-related pathways. Based on the docking results and traditional therapeutic values, a polyherbal formulation (PHF) was developed using methanolic extracts of Trigonella foenum-graecum, Emblica officinalis, Pterocarpus marsupium, Withania somnifera, Asparagus racemosus, Zingiber officinale, Rubia cordifolia, Boerhavia diffusa, and Adhatoda vasica. Phytochemical screening via HPTLC analysis was used to quantify the presence of gallic and ellagic acids. In addition, PHF showed significant antioxidant potential (DPPH IC50: 14.29 µg/mL; FRAP IC50: 58.57 µg/mL) and iron content (98.47 ppm) values. Furthermore, in vivo evaluation using a phenylhydrazine-induced hemolytic anemia model in Sprague Dawley rats revealed that the PHF achieved complete restoration of RBCs (6.15 ± 0.04), hemoglobin (14.82 ± 0.03 g/dL), and hematocrit (43.08 ± 0.28%) in anemic rats and improved histopathological features in the liver, spleen, and bone marrow. These results demonstrate that combined molecular and pharmacological evidence support the efficacy of PHF as a promising candidate for the management of anemia by enhancing erythropoiesis, improving iron metabolism, and reducing oxidative stress. Full article
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15 pages, 4060 KB  
Article
Attenuation Effect of Withania somnifera Extract on Restraint Stress-Induced Anxiety-like Behavior and Hippocampal Alterations in Mice
by Kippuem Lee, Daehyeop Lee, Joo Yun Kim, Jae Jung Shim, Jae Woo Bae and Jae Hwan Lee
Int. J. Mol. Sci. 2025, 26(15), 7317; https://doi.org/10.3390/ijms26157317 - 29 Jul 2025
Cited by 2 | Viewed by 2268
Abstract
Stress is a major factor that threatens the body’s homeostasis or well-being. Excessive stress causes psychological anxiety and tension, which disrupts the balance of the autonomic nervous system that maintains the body’s balance, resulting in hormonal imbalance and brain changes. In this study, [...] Read more.
Stress is a major factor that threatens the body’s homeostasis or well-being. Excessive stress causes psychological anxiety and tension, which disrupts the balance of the autonomic nervous system that maintains the body’s balance, resulting in hormonal imbalance and brain changes. In this study, we investigated the effects of Withania somnifera (Ashwagandha) extract on depression, neurobehavior, and hippocampal changes in model mice exposed to stress. Using an excessive restraint stress-induced depression model, we measured the behavioral changes and the levels of brain-derived neurotrophic factor (BDNF) and antioxidant genes in five groups: control, stress, low-dose W. somniferous extract (20 mg/kg/day), high-dose W. somniferous extract (40 mg/kg/day), and L-theanine (50 mg/kg/day, positive control). Stressed mice showed poorer performance in the open field and elevated plus maze tests compared with the control group. The impaired performance was restored following W. somniferous extract administration. In addition, W. somniferous extract restored the decreased expression of BDNF in the hippocampus caused by restraint stress, improved the balance of stress hormones (i.e., cortisol, dopamine, and norepinephrine), and also regulated BDNF, inflammatory genes, and antioxidant genes in brain tissue. Therefore, W. somniferous extract can induce antidepressant and anti-stress effects by maintaining brain BDNF expression and preventing hippocampal tissue alterations caused by restraint stress. Full article
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33 pages, 10543 KB  
Article
Withania somnifera Ameliorates Doxorubicin-Induced Nephrotoxicity and Potentiates Its Therapeutic Efficacy Targeting SIRT1/Nrf2, Oxidative Stress, Inflammation, and Apoptosis
by Amany Mohammed Mohmmed Hegab, Soha Osama Hassanin, Reham Hassan Mekky, Samah Sulaiman Abuzahrah, Alaaeldin Ahmed Hamza, Iman M. Talaat and Amr Amin
Pharmaceuticals 2025, 18(2), 248; https://doi.org/10.3390/ph18020248 - 12 Feb 2025
Cited by 31 | Viewed by 5150
Abstract
Background: Doxorubicin (DOX) is a very powerful chemotherapy drug. However, its severe toxicity and potential for resistance development limit its application. Withania somnifera L. Dunal (WIT) has therapeutic capacities, including anti-inflammatory, antioxidant, and anticancer activities. This study investigates the preventative benefits of [...] Read more.
Background: Doxorubicin (DOX) is a very powerful chemotherapy drug. However, its severe toxicity and potential for resistance development limit its application. Withania somnifera L. Dunal (WIT) has therapeutic capacities, including anti-inflammatory, antioxidant, and anticancer activities. This study investigates the preventative benefits of a standardized WIT extract against DOX-induced renal damage in vivo. We also investigate the synergistic effects of combining WIT and DOX to improve therapeutic efficacy in breast cancer cells (MCF7-ADR). Methods: This study employed an animal model where rats were administered 300 mg/kg/day of WIT orally for a duration of 14 days. Rats received DOX injections at a dose of 5 mg/kg, for a total of 15 mg, on the 6th, 8th, and 10th days. Results: Present results revealed that WIT reduced DOX-induced increase levels of blood urea and creatinine and the activity of kidney injury molecule-1. WIT also reduced renal tissue damage, oxidative stress, and levels of pro-inflammatory markers. WIT alleviated the effects of DOX on nuclear factor erythroid 2-related factor 2, heme oxygenase-1, and sirtuin 1 in the renal tissues. WIT modulated nuclear factor-κB activity and decreased apoptotic indicators. Furthermore, WIT improves DOX’s capacity to kill drug-resistant MCF7-ADR cells by arresting the cell cycle and promoting apoptosis. Chemical analysis of WIT root extract revealed 34 distinct compounds, including alkaloids, withanolides, flavanones, and fatty acids. Conclusions: These constituents synergistically contribute to WIT’s antioxidant, anti-inflammatory, and anti-apoptotic properties. In addition, they confirm its ability to reduce systemic toxicity while improving treatment efficacy. Full article
(This article belongs to the Section Pharmacology)
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21 pages, 9442 KB  
Article
Ashwagandha: Optimizing the Extraction and Electrospun Nanofiber Production
by Maciej Jaskólski, Magdalena Paczkowska-Walendowska, Andrzej Miklaszewski and Judyta Cielecka-Piontek
Pharmaceutics 2025, 17(1), 61; https://doi.org/10.3390/pharmaceutics17010061 - 5 Jan 2025
Cited by 5 | Viewed by 3130
Abstract
Background/Objectives: This study explores the development of electrospun nanofibers incorporating bioactive compounds from Withania somnifera (Ashwagandha) root extract, focusing on optimizing extraction conditions and nanofiber composition to maximize biological activity and application potential. Methods: Using the Design of Experiment (DoE) approach, optimal extraction [...] Read more.
Background/Objectives: This study explores the development of electrospun nanofibers incorporating bioactive compounds from Withania somnifera (Ashwagandha) root extract, focusing on optimizing extraction conditions and nanofiber composition to maximize biological activity and application potential. Methods: Using the Design of Experiment (DoE) approach, optimal extraction parameters were identified as 80% methanol, 70 °C, and 60 min, yielding high levels of phenolic compounds and antioxidant activity. Methanol concentration emerged as the critical factor influencing phytochemical properties. Electrospinning technology was employed to produce nanofibers using polyvinylpyrrolidone (PVP) and hydroxypropyl-β-cyclodextrin (HPβCD) as carriers, ensuring encapsulation, stabilization, and an enhanced bioavailability of the active compounds. Results: Nanofibers demonstrated a high surface-to-volume ratio, rapid dissolution, and significant mucoadhesive properties, making them suitable for oral mucosal applications. The optimal nanofiber composition was determined to be 2.5 mL extract, 25% PVP, and an extract-to-HPβCD ratio of 1:0.6. Statistical modeling confirmed that the electrospinning process did not compromise the antioxidant or anti-inflammatory properties of the extract, with extract content being the primary determinant of biological activity. Conclusions: These findings highlight the potential of integrating advanced extraction techniques with nanotechnology to develop innovative delivery systems for traditional herbal remedies. The developed nanofibers offer promising applications in pharmaceuticals, cosmetics, and functional foods, paving the way for a scalable and efficient utilization of Ashwagandha bioactives. Full article
(This article belongs to the Special Issue Electrospinning in Drug Delivery Applications)
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30 pages, 1570 KB  
Review
Quantifying Withanolides in Plasma: Pharmacokinetic Studies and Analytical Methods
by Alex B Speers, Axel Lozano-Ortiz and Amala Soumyanath
Nutrients 2024, 16(22), 3836; https://doi.org/10.3390/nu16223836 - 8 Nov 2024
Cited by 9 | Viewed by 8962
Abstract
Withania somnifera (common name: ashwagandha; WS) is an Ayurvedic botanical that has become popular for its reputed effects on stress and insomnia. Research into the bioactive compounds responsible for the biological effects of WS has largely focused on withanolides, a group of steroidal [...] Read more.
Withania somnifera (common name: ashwagandha; WS) is an Ayurvedic botanical that has become popular for its reputed effects on stress and insomnia. Research into the bioactive compounds responsible for the biological effects of WS has largely focused on withanolides, a group of steroidal lactones commonly found in the Solanaceae family. Until recently, however, it was unclear which, if any, withanolides were present in the plasma after the ingestion of WS products. The aim of this review is to summarize current knowledge regarding the plasma pharmacokinetics of withanolides found in WS and the analytical methods developed to detect them in plasma. Twenty studies (sixteen animal, four human) were identified in which isolated withanolides or withanolide-containing products were administered to animals or humans and quantified in plasma. Withanolides were commonly analyzed using reversed-phase liquid chromatography coupled to mass spectrometry. Plasma concentrations of withanolides varied significantly depending on the substance administered, withanolide dose, and route of administration. Plasma pharmacokinetics of withaferin A, withanolide A, withanolide B, withanoside IV, 12-deoxywithastramonolide, and withanone have been reported in rodents (Cmax range: 5.6–8410 ng/mL), while withaferin A, withanolide A, 12-deoxywithastramonolide, and withanoside IV pharmacokinetic parameters have been described in humans (Cmax range: 0.1–49.5 ng/mL). Full article
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11 pages, 906 KB  
Article
Phytochemical Screening and Characterization of Volatile Compounds from Three Medicinal Plants with Reported Anticancer Properties Using GC-MS
by Emelinah Mathe, Lesibana Sethoga, Sipho Mapfumari, Oluwaseyefunmi Adeniran, Phineas Mokgotho, Jerry Shai and Stanley Gololo
Life 2024, 14(11), 1375; https://doi.org/10.3390/life14111375 - 25 Oct 2024
Cited by 7 | Viewed by 5853
Abstract
Annona senegalensis pers, Sutherlandia frutescens (L.), and Withania somnifera (L.) are abundant plants and widely distributed in the Limpopo, Gauteng, Kwazulu-Natal, North West and Mpumalanga provinces in South Africa. The three plants are among those used by traditional healers and herbalists in [...] Read more.
Annona senegalensis pers, Sutherlandia frutescens (L.), and Withania somnifera (L.) are abundant plants and widely distributed in the Limpopo, Gauteng, Kwazulu-Natal, North West and Mpumalanga provinces in South Africa. The three plants are among those used by traditional healers and herbalists in South Africa for the treatment of a variety of diseases, including cancer. The current study aimed at the phytochemical screening and characterization of volatile compounds from the three medicinal plants using GC-MS. The methanol leaf extracts were subjected to phytochemical screening using standard chemical tests to detect the presence of different classes of compounds. Volatile compounds were detected by GC-MS analysis, and detected compounds were identified by comparing the MS spectral data with those of compounds deposited in the NIST Library (NIST08). Phytochemical screening indicated the presence of different secondary metabolites such as alkaloids, quinones, steroids, cardiac glycosides, coumarins, and terpenoids in all plants. GC-MS chromatograms allowed the detection and identification of 19 volatile compounds among the three plants with known bioactivities that are important in the management of life-threatening diseases such as cancer and diabetes. The results confirm the leaves of Annona senegalensis, Sutherlandia frutescens, and Withania somnifera as sources of important phytochemicals and therefore justify their use for the treatment of various diseases by traditional healers. Full article
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15 pages, 3956 KB  
Article
Withania somnifera (Ashwagandha) Improves Spatial Memory, Anxiety and Depressive-like Behavior in the 5xFAD Mouse Model of Alzheimer’s Disease
by Noah Gladen-Kolarsky, Olivia Monestime, Melissa Bollen, Jaewoo Choi, Liping Yang, Armando Alcazar Magaña, Claudia S. Maier, Amala Soumyanath and Nora E. Gray
Antioxidants 2024, 13(10), 1164; https://doi.org/10.3390/antiox13101164 - 25 Sep 2024
Cited by 13 | Viewed by 9594
Abstract
Withania somnifera (WS), also known as ashwagandha, is a popular botanical supplement used to treat various conditions including memory loss, anxiety and depression. Previous studies from our group showed an aqueous extract of WS root (WSAq) enhances cognition and alleviates markers for depression [...] Read more.
Withania somnifera (WS), also known as ashwagandha, is a popular botanical supplement used to treat various conditions including memory loss, anxiety and depression. Previous studies from our group showed an aqueous extract of WS root (WSAq) enhances cognition and alleviates markers for depression in Drosophila. Here, we sought to confirm these effects in the 5xFAD mouse model of β-amyloid (Aβ) accumulation. Six- to seven-month-old male and female 5xFAD mice were treated with WSAq in their drinking water at 0 mg/mL, 0.5 mg/mL or 2.5 mg/mL for four weeks. In the fourth week of treatment, spatial memory, anxiety and depressive-like symptoms were evaluated. At the conclusion of behavioral testing, brain tissue was harvested, immunohistochemistry was performed, and the cortical expression of antioxidant response genes was evaluated. Both concentrations of WSAq improved spatial memory and reduced depressive and anxiety-related behavior. These improvements were accompanied by a reduction in Aβ plaque burden in the hippocampus and cortex and an attenuation of activation of microglia and astrocytes. Antioxidant response genes were upregulated in the cortex of WSAq-treated mice. Oral WSAq treatment could be beneficial as a therapeutic option in AD for improving disease pathology and behavioral symptoms. Future studies focused on dose optimization of WSAq administration and further assessment of the mechanisms by which WSAq elicits its beneficial effects will help inform the clinical potential of this promising botanical therapy. Full article
(This article belongs to the Special Issue Oxidative-Stress in Human Diseases—3rd Edition)
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17 pages, 657 KB  
Article
Circular Economy, Dairy Cow Feed Leftovers, and Withania somnifera Supplementation: Effects on Black Belly Ram’s Libido, Sperm Quality, Sexual Behavior, and Hemogram Values
by Andrés J. Rodriguez-Sánchez, Cesar A. Meza-Herrera, Angeles De Santiago-Miramontes, Cayetano Navarrete-Molina, Francisco G. Veliz-Deras, Julieta Z. Ordoñez-Morales, Jessica M. Flores-Salas and Ruben I. Marin-Tinoco
Biology 2024, 13(9), 656; https://doi.org/10.3390/biology13090656 - 24 Aug 2024
Cited by 5 | Viewed by 2219
Abstract
Considering a circular economy perspective, this study evaluates the possible effect of targeted short-term supplementation with Withania somnifera L. (WS; Ashwagandha) on ram’s seminal quality, socio-sexual behaviors, and blood constituents. Black Belly rams (n = 20) received a basal diet comprising feed-leftovers from [...] Read more.
Considering a circular economy perspective, this study evaluates the possible effect of targeted short-term supplementation with Withania somnifera L. (WS; Ashwagandha) on ram’s seminal quality, socio-sexual behaviors, and blood constituents. Black Belly rams (n = 20) received a basal diet comprising feed-leftovers from dairy cows in the north-arid Mexico (i.e., Comarca Lagunera CL). The experimental units, with proven libido and fertility, were homogeneous in terms of age (3.41 ± 0.21 yr.), live weight (LW; 53.8 ± 3.3 kg), body condition (BC; 2.96 ± 0.01 units), initial sperm concentration (2387 ± 804 × 106), and viability (23.9 ± 15.6%). Rams were randomly assigned during the transition reproductive period (i.e., May to Jun; 25° NL) to three treatment groups: non-supplemented control group (CONT; n = 6), low WS-supplemented (LWS; i.e., 100 mg kg LW−1 d−1 × 40 d; n = 7), and high-WS-supplemented (HWS; i.e., 200 mg kg LW−1 d−1 × 40 d; n = 7). The basal leftover diet was offered twice daily (0700 and 1600 h); the experimental period (EP) lasted 47 d. No differences (p > 0.05) among treatments occurred regarding LW and BCS at the onset of the EP. Whereas the greater scrotal circumference (SCRC, cm) arose in the LWS and CONT rams, an increased ejaculated volume (VOLEJA, mL) occurred in the WS-rams. A total of 5/9 (i.e., 55%) appetitive and 3/3 (i.e., 100%) consummatory sexual behaviors favored (p < 0.05) the WS-rams, particularly the HWS rams, towards the final EP. The same was true (p < 0.05) regarding the hemogram variables white blood cell count (×109 cells L−1), hemoglobin concentration (g dL−1), and medium corpuscular volume (fL). This study, based on a rethink–reuse–reduce enquiry approach, enabled connectedness between two noteworthy animal systems in the CL: dairy cows and meat sheep schemes. Certainly, the use of dairy cow feed-leftovers aligned with the short-term supplementation with WS promoted enhanced testicular function, augmented seminal volume, and an increased sexual behavior in Black Belly rams in northern Mexico. Finally, while our research outcomes should enhance not only the resilience and sustainability of sheep production and the well-being of sheep-producers and their families, it may also embrace clinical translational applications. Full article
(This article belongs to the Special Issue Reproductive Management of Goats and Sheep)
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